Yield of genetic testing in hypertrophic cardiomyopathy

Mayo Clin Proc. 2005 Jun;80(6):739-44. doi: 10.1016/S0025-6196(11)61527-9.


Objective: To determine the clinical parameters of hypertrophic cardiomyopathy (HCM) that correlated significantly with the presence of an identifiable sarcomeric mutation.

Patients and methods: Previous comprehensive mutational analyses of all protein-coding exons of 8 sarcomeric genes revealed pathogenic mutations in 147 (38%) of 389 unrelated patients seen at the HCM outpatient clinic at the Mayo Clinic in Rochester, Minn, between April 1997 and December 2001. Clinical data, extracted from patient records and blinded to patient genotype, were maintained in a custom database.

Results: In 389 unrelated patients, younger age at diagnosis, family history of HCM, and Increasing left ventricular wall thickness were all associated with Increased likelihood of identifying an HCM-associated sarcomeric mutation. In contrast, family history of sudden cardiac death, myectomy status, and anatomical subtype did not correlate significantly with genotype-positive status. With use of a simple scoring system based on age at diagnosis, left ventricular wall thickness, and family history of HCM, the likelihood of a sarcomeric mutation could be estimated.

Conclusion: Clinical predictors of positive genotype, such as the presence of an implantable cardioverter-defibrillator, age at diagnosis, degree of left ventricular wall hypertrophy, and family history of HCM, may aid in patient selection for genetic testing and increase the yield of cardiac sarcomere gene screening.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Cardiomyopathy, Hypertrophic / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Techniques*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation
  • Predictive Value of Tests
  • Retrospective Studies
  • Sarcomeres / genetics*